Non-proliferative Diabetic Retinopathy
Conditions
Keywords
Non-proliferative Diabetic Retinopathy, Diabetic Retinopathy, NPDR, KSI-301, VEGF, Anti-VEGF, Vascular Endothelial Growth Factor, Antibody Biopolymer Conjugate, Retinal Degeneration, Retinal Diseases, Eye Diseases, Retinopathy, Vision Disorders, Kodiak
Brief summary
This Phase 3 Study will evaluate the efficacy and safety of KSI-301 in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
Detailed description
This is a Phase 3, prospective, randomized, double-masked, sham-controlled, two-arm, multicenter study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR). The primary endpoint will be assessed at Week 48; additional secondary endpoints for efficacy will be assessed at Week 48, Week 96 and if applicable, over time.
Interventions
DRUGKSI-301
Intravitreal injection
OTHERSham injection
The sham injection is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It is performed to maintain masking of the study.
Sponsors
Kodiak Sciences Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
To preserve masking, 2 investigators are required for this study. The masked investigator will be responsible for examinations and safety assessments. The unmasked investigator will perform the injections and post-treatment assessments.
Intervention model description
Participants will be randomized 1:1 into one of two arms: KSI-301 or sham.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to participation in the study. * Type 1 or 2 diabetes mellitus * Moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center), in which pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator. * BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better) * HbA1c of ≤12%. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Presence of center-involved DME in the Study Eye * Prior PRP in the Study Eye. * Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye. * Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME. * Prior intravitreal or periocular steroid in the Study Eye for DR or DME. * Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye. * Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study * Active or suspected ocular or periocular infection or inflammation. * Women who are pregnant or lactating or intending to become pregnant during the study. * History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. * Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event. * Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Improving ≥2 Steps on DRSS | Day 1 to Week 48 | Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | Day 1 to Week 48 | Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48 |
| Time to First Development of PDR, ASNV, or DME | Day 1 to Week 48 | Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), or Diabetic Macular Edema (DME) through Week 48 |
| Time to First Development of PDR or ASNV | Day 1 to Week 48 | Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) through Week 48 |
| Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | Day 1 to Week 48 | Time to first development of vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48 |
| Percentage of Patients Developing Any Sight-Threatening Complication | Day 1 to Week 48 | Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48 |
| Percentage of Patients Improving ≥3 Steps on DRSS | Day 1 to Week 48 | Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). |
| Percentage of Patients Developing PDR | Day 1 to Week 48 | Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48 |
| Percentage of Patients Developing PDR or ASNV | Day 1 to Week 48 | Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48 |
| Percentage of Patients Developing DME | Day 1 to Week 48 | Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48 |
| Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS | Day 1 to Week 48 | Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). |
| Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Day 1 to Week 48 | Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in BCVA | Day 1 to Week 48 | Mean change in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. |
| Time to First Development of DME | Day 1 to Week 48 | Time to first development of Diabetic Macular Edema (DME) through Week 48 |
| Mean Change in OCT CST | Day 1 to Week 48 | Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time |
Countries
Czechia, Latvia, Poland, Puerto Rico, Slovakia, Spain, United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 52 medical centers between September 2021 and August 2022. The first participant was enrolled on 07 September 2021 and the last on 25 August 2022.
Pre-assignment details
Of 560 screened participants, 253 met eligibility criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| KSI-301 - Treatment Group A Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92
KSI-301: Intravitreal injection | 128 |
| Treatment Group B Sham injection on the same schedule as Treatment Group A
Sham injection: The sham injection is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It is performed to maintain masking of the study. | 125 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| After Week 48 | Adverse Event | 1 | 0 |
| After Week 48 | Lost to Follow-up | 3 | 3 |
| After Week 48 | Non-compliance with study schedule | 1 | 0 |
| After Week 48 | Sponsor Request | 115 | 111 |
| After Week 48 | Withdrawal by Subject | 0 | 1 |
| Primary Study (Through Week 48) | Adverse Event | 1 | 4 |
| Primary Study (Through Week 48) | Lost to Follow-up | 2 | 3 |
| Primary Study (Through Week 48) | Non-compliance with study schedule | 0 | 1 |
| Primary Study (Through Week 48) | Participant relocated | 1 | 0 |
| Primary Study (Through Week 48) | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Treatment Group B | Total | KSI-301 - Treatment Group A |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 62 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 95 Participants | 191 Participants | 96 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 9.63 | 56.7 years STANDARD_DEVIATION 10.54 | 56.4 years STANDARD_DEVIATION 11.39 |
| Diabetic Retinopathy Severity Scale (DRSS) at Baseline DRSS Level ≤47 | 45 Participants | 91 Participants | 46 Participants |
| Diabetic Retinopathy Severity Scale (DRSS) at Baseline DRSS Level ≥53 | 80 Participants | 162 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 109 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 144 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region North America | 120 Participants | 243 Participants | 123 Participants |
| Geographic Region Rest of World | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 36 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 96 Participants | 204 Participants | 108 Participants |
| Sex: Female, Male Female | 56 Participants | 107 Participants | 51 Participants |
| Sex: Female, Male Male | 69 Participants | 146 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 128 | 1 / 125 | 1 / 120 | 0 / 115 |
| other Total, other adverse events | 49 / 128 | 51 / 125 | 15 / 120 | 9 / 115 |
| serious Total, serious adverse events | 18 / 128 | 12 / 125 | 8 / 120 | 3 / 115 |
Outcome results
Primary
Percentage of Patients Improving ≥2 Steps on DRSS
Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Improving ≥2 Steps on DRSS | 52 Participants |
| Treatment Group B | Percentage of Patients Improving ≥2 Steps on DRSS | 2 Participants |
p-value: <0.000195.02% CI: [31.3, 48.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Developing Any Sight-Threatening Complication
Percentage of patients developing any of the following Sight-Threatening Complication: Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), Vitreous hemorrhage or tractional retinal detachment believed to be due to PDR, or Diabetic Macular Edema (DME) from baseline through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Developing Any Sight-Threatening Complication | 3 Participants |
| Treatment Group B | Percentage of Patients Developing Any Sight-Threatening Complication | 26 Participants |
p-value: <0.000195.02% CI: [-26.2, -11.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Developing DME
Percentage of patients developing Diabetic Macular Edema (DME) from baseline through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Developing DME | 1 Participants |
| Treatment Group B | Percentage of Patients Developing DME | 17 Participants |
Secondary
Percentage of Patients Developing PDR
Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Developing PDR | 2 Participants |
| Treatment Group B | Percentage of Patients Developing PDR | 10 Participants |
p-value: 0.014995.02% CI: [-11.8, -1.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Developing PDR or ASNV
Percentage of patients developing Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) from baseline through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Developing PDR or ASNV | 2 Participants |
| Treatment Group B | Percentage of Patients Developing PDR or ASNV | 10 Participants |
Secondary
Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR
Percentage of patients developing vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) from baseline through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | 2 Participants |
| Treatment Group B | Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | 3 Participants |
Secondary
Percentage of Patients Improving ≥3 Steps on DRSS
Percentage of patients improving ≥3 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Improving ≥3 Steps on DRSS | 7 Participants |
| Treatment Group B | Percentage of Patients Improving ≥3 Steps on DRSS | 0 Participants |
p-value: 0.005895.02% CI: [1.6, 9.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA
Percentage of patients who lost ≥5, ≥10, or ≥15 letters in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. The Overall Number of Participants Analyzed were 128 and 125, but the number analyzed for each row is different depending on the number of participants with data for that row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 8 | 8 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 20 | 15 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 32 | 17 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 20 | 1 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 44 | 12 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 48 | 14 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 8 | 2 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 20 | 2 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 32 | 5 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 44 | 4 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 48 | 5 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 8 | 1 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 32 | 4 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 44 | 0 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 48 | 3 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 20 | 1 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 8 | 15 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 32 | 1 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 20 | 15 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 44 | 0 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 44 | 2 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 32 | 10 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 32 | 0 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 44 | 8 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 48 | 1 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 5 letters from baseline to Week 48 | 11 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 48 | 0 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 8 | 3 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 15 letters from baseline to Week 8 | 1 Participants |
| Treatment Group B | Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA | Participants who lost ≥ 10 letters from baseline to Week 20 | 4 Participants |
Secondary
Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS
Percentage of patients with a ≥2-step or ≥3-step worsening on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KSI-301 - Treatment Group A | Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS | Patients with a ≥3-step worsening on DRSS | 0 Participants |
| KSI-301 - Treatment Group A | Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS | Patients with a ≥2-step worsening on DRSS | 1 Participants |
| Treatment Group B | Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS | Patients with a ≥3-step worsening on DRSS | 3 Participants |
| Treatment Group B | Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS | Patients with a ≥2-step worsening on DRSS | 5 Participants |
Secondary
Time to First Development of PDR, ASNV, or DME
Time to first development of Proliferative Diabetic Retinopathy (PDR), Anterior segment neovascularization (ASNV), or Diabetic Macular Edema (DME) through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KSI-301 - Treatment Group A | Time to First Development of PDR, ASNV, or DME | NA Months |
| Treatment Group B | Time to First Development of PDR, ASNV, or DME | NA Months |
Secondary
Time to First Development of PDR or ASNV
Time to first development of Proliferative Diabetic Retinopathy (PDR) or Anterior segment neovascularization (ASNV) through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KSI-301 - Treatment Group A | Time to First Development of PDR or ASNV | NA Months |
| Treatment Group B | Time to First Development of PDR or ASNV | NA Months |
Secondary
Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR
Time to first development of vitreous hemorrhage or tractional retinal detachment believed to be due to Proliferative Diabetic Retinopathy (PDR) through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KSI-301 - Treatment Group A | Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | NA Months |
| Treatment Group B | Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR | NA Months |
Other Pre-specified
Mean Change in BCVA
Mean change in Best-corrected Visual Acuity (BCVA) from baseline by visit over time. Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. The Overall Number of Participants Analyzed were 128 and 125, but the number analyzed for each row is different depending on the number of participants with data for that row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KSI-301 - Treatment Group A | Mean Change in BCVA | Week 20 | 1.1 ETDRS Letters | Standard Deviation 5.22 |
| KSI-301 - Treatment Group A | Mean Change in BCVA | Week 44 | 1.0 ETDRS Letters | Standard Deviation 5.63 |
| KSI-301 - Treatment Group A | Mean Change in BCVA | Week 32 | 0.9 ETDRS Letters | Standard Deviation 8.68 |
| KSI-301 - Treatment Group A | Mean Change in BCVA | Week 48 | 1.1 ETDRS Letters | Standard Deviation 6.44 |
| KSI-301 - Treatment Group A | Mean Change in BCVA | Week 8 | 1.3 ETDRS Letters | Standard Deviation 5.02 |
| Treatment Group B | Mean Change in BCVA | Week 48 | 1.5 ETDRS Letters | Standard Deviation 5.49 |
| Treatment Group B | Mean Change in BCVA | Week 8 | 0.2 ETDRS Letters | Standard Deviation 4.8 |
| Treatment Group B | Mean Change in BCVA | Week 20 | 0.3 ETDRS Letters | Standard Deviation 6.29 |
| Treatment Group B | Mean Change in BCVA | Week 32 | 1.2 ETDRS Letters | Standard Deviation 4.87 |
| Treatment Group B | Mean Change in BCVA | Week 44 | 1.6 ETDRS Letters | Standard Deviation 5.55 |
Other Pre-specified
Mean Change in OCT CST
Mean change in Optical Coherence Tomography (OCT) central subfield retinal thickness (CST) from baseline by visit over time
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KSI-301 - Treatment Group A | Mean Change in OCT CST | Week 20 | -12.8 Microns | Standard Deviation 13.42 |
| KSI-301 - Treatment Group A | Mean Change in OCT CST | Week 44 | -8.9 Microns | Standard Deviation 19.71 |
| KSI-301 - Treatment Group A | Mean Change in OCT CST | Week 32 | -13.9 Microns | Standard Deviation 14.88 |
| KSI-301 - Treatment Group A | Mean Change in OCT CST | Week 48 | -15.2 Microns | Standard Deviation 16.35 |
| KSI-301 - Treatment Group A | Mean Change in OCT CST | Week 8 | -9.8 Microns | Standard Deviation 10.64 |
| Treatment Group B | Mean Change in OCT CST | Week 48 | -0.7 Microns | Standard Deviation 15.76 |
| Treatment Group B | Mean Change in OCT CST | Week 8 | 4.5 Microns | Standard Deviation 17.22 |
| Treatment Group B | Mean Change in OCT CST | Week 20 | 6.6 Microns | Standard Deviation 28.99 |
| Treatment Group B | Mean Change in OCT CST | Week 32 | 5.2 Microns | Standard Deviation 27.86 |
| Treatment Group B | Mean Change in OCT CST | Week 44 | -0.5 Microns | Standard Deviation 17.12 |
Other Pre-specified
Time to First Development of DME
Time to first development of Diabetic Macular Edema (DME) through Week 48
Time frame: Day 1 to Week 48
Population: Full analysis set defined as all randomized subjects who received any study treatment (KSI-301 or sham) and have gradable DRSS value at baseline. Subjects will be analyzed according to their randomized treatment. Subjects who did not have an event were censored at the date of the last scheduled study visit at or prior to Week 48.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KSI-301 - Treatment Group A | Time to First Development of DME | NA Months |
| Treatment Group B | Time to First Development of DME | NA Months |